Cystinuria: Defective Intestinal Transport of Dibasic Amino Acids and Cystine*

The clinical manifestations of cystinuria are lo- calized to the urinary tract and result from the formation of cystine calculi.The findings of in- creased excretion of cystine, lysine, arginine, and ornithine in the urine at a time when the plasma levels of these amino acids were normal or low suggested to Dent and Rose (2) that a renal tu- 1)ular reabsorptive site, shared by the involved amino acids, was defective.Investigations from our laboratory (3), using slices of human kidney, failed to confirm the hypothesis of Dent and Rose.Cystine did not compete with the dibasic amino acids in vitro, and although the transport of ly- sine and arginine was defective in cystinuria, cys- tine transport was unimpaired.Although evidence had been accumulating for over 60 years (4-6), it was not until 1960 that the concept of an intestinal transport defect in cystinuria emerged.Milne, Asatoor, and co- workers (7, 8) noted that urinary and fecal ex- cretion of the diamines, cadaverine and putrescine, was elevated in cystinuric subjects fed lysine and ornithine, respectively.These diamines are formed by bacterial decarboxylation of the dibasic amino acids.Hence, it was postulated that lysine and ornithine were poorly absorbed from the small intestine in cystinuria and were presented to colonic bacteria in increased amounts, result- ing in excessive diamine formation and excretion.